Comparison of Diagnostic Rates and Concordance with Subsequent Surgical Resections between Conventional Smear and ThinPrep Preparations versus ThinPrep Only in Thyroid Fine Needle Aspiration (T-FNA) Specimens.

BACKGROUND: Thyroid fine needle aspiration (T-FNA) is a mainstay in management of thyroid nodules. However, the preparation of T-FNA specimens varies across institutions. Prior studies have compared diagnostic rates between different specimen preparations of T-FNA specimens and their associated advantages and disadvantages. However, few have compared the rates of all diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) between liquid-based preparations (LBPs) and a combination of LBP and conventional smear (CS) preparations. Our study compares TBSRTC diagnostic rates between these 2 cohorts and correlates cytologic diagnoses with subsequent thyroid resections to evaluate rates of neoplasia (RON) and malignancy (ROM). METHODS: 584 consecutive thyroid FNA specimens were collected and stratified by preparation type (ThinPrep [TP] vs. CS & TP). Diagnostic rates for each TBSRTC diagnostic category were calculated. The institution's electronic medical records database was searched for histologic diagnoses of previously sampled thyroid nodules to evaluate the RON and ROM. RESULTS: Of 584 thyroid FNA specimens, 73 (12.5%) and 511 (87.5%) were evaluated by TP only and CS & TP, respectively, reflecting the predominance of rapid on-site evaluation (ROSE) with CS for T-FNAs at our institution. Of the TP only and CS & TP cohorts, 29 (39.7%) and 98 (19.2%) had subsequent resections, respectively. The frequency of non-diagnostic cases was lower in the CS & TP cohort (12.7% vs. 26%). While the diagnostic rate of follicular lesion of undetermined significance was similar for both cohorts, SFN categorization was only utilized in the CS & TP cohort (1.5% vs. 0%). Although RON and ROM were similar between cohorts in many of the TBSRTC categories, there was a higher RON associated with non-diagnostic specimens in the TP only cohort when the denominator included all non-diagnostic cases. CONCLUSION: The combination of CS and LBP may potentially decrease the non-diagnostic rate of T-FNA specimens as well as the number of passes required for diagnosis, particularly with ROSE. Evaluation of morphologic features highlighted in conventional smears may facilitate diagnostic categorization in the "suspicious for follicular neoplasm" category.

An institutional experience: A retrospective analysis of the effect of transitioning from follicular lesion of undetermined significance to atypia of undetermined significance with subclassified atypia on interobserver concordance, rates of neoplasia, and rates of malignancy.

INTRODUCTION: The rate of malignancy (ROM) in thyroid fine needle aspirations (FNA) classified under "atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), including Hürthle cell type (HLUS)" category of The Bethesda system for reporting thyroid cytopathology (TBSRTC) in literature is highly variable. The 2018 TBSRTC was updated to note a preferred categorization of AUS cases into subcategories. This study evaluates the impact of AUS subclassification on rates of neoplasia (RON), rates of malignancy (ROM), and cytopathologist (CP) concordance. METHODS: 93 thyroid FNAs previously diagnosed as FLUS or HLUS from January 1, 2013 to December 31, 2014 with subsequent surgical resection were identified. Four CPs reclassified these cases using TBSRTC AUS subcategories of follicular cells with architectural and/or cytologic atypia, predominantly Hürthle cells, and atypical lymphocytes. RON and ROM were calculated for each diagnostic subcategory for each CP. RESULTS: The original RON and ROM for FLUS cases were 31.4% and 15.1% and were 77.8% and 22.2% for HLUS cases. 10.8% of cases showed diagnostic concordance amongst the four CPs. The most frequently utilized subcategory was architectural atypia. RON ranges for architectural atypia, cytologic atypia, architectural and cytologic atypia, and predominantly Hürthle cells were 28.1% to 35.7%, 0% to 33.3%, 35.3% to 66.7%, and 57.1% to 87.5%. The range of ROM was 13.9% to 16.7%, 0% to 33%, 0% to 42.9%, and 0% to 25%, respectively. CONCLUSION: RON for AUS predominantly Hürthle cells subcategory was higher than previously reported, which may indicate use for tailored patient management pathways. AUS subclassification can result in significant interobserver variability. Therefore, institutions may consider consensus/quality control sessions to optimize diagnostic concordance.

Radiation-Induced Skin Changes after Postmastectomy Radiation Therapy: A Pilot Study on Indicators for Timing of Delayed Breast Reconstruction.

BACKGROUND: Delayed autologous breast reconstruction is commonly recommended in patients requiring postmastectomy radiation. This study examines gross and histologic changes in the breast skin of patients who have undergone postmastectomy radiation to help determine when radiation-induced skin changes begin to stabilize. METHODS: A prospective pilot study was conducted on eight patients with invasive breast cancer who required mastectomy and radiotherapy. At the time of mastectomy and 2, 4, 6, 8, and 12 months after completion of radiotherapy, a punch biopsy was taken from the radiated mastectomy skin of each patient. Serial standardized photographs were taken before and after radiotherapy to evaluate the degree of hyperpigmentation and graded by three blinded plastic surgeons. Skin biopsies were processed for histologic assessment of inflammation, elastin organization, and vascularity. RESULTS: Grading of patient photographs revealed an increase in hyperpigmentation after radiotherapy compared with baseline with a gradual improvement over time. SMAD3 immunostaining demonstrated a trend toward an increase in inflammation over 12 months. The elastin distribution within samples showed an increase in fiber disorganization, thickening, and clumping, with no improvement throughout the study period. The average number of vessels per high powered field decreased steadily through the duration of the study. CONCLUSION: Histologic changes in dermal inflammation, elastin organization, and vascularity do not appear to correspond with the gradual improvement of hyperpigmentation, resulting from postmastectomy radiation. These histologic changes persist beyond the 12 month observation period and will require clinical correlation to determine the potential impact on postoperative outcomes.

Characteristics of a Breast Pathology Consultation Practice.

CONTEXT: - Intradepartmental consultation is a routine practice commonly used for new diagnoses. Expert interinstitutional case review provides insight into particularly challenging cases. OBJECTIVE: - To investigate the practice of breast pathology consultation at a large tertiary care center. DESIGN: - We reviewed breast pathology cases sent for private consultation and internal cases reviewed by multiple pathologists at a tertiary center. Requisitions and reports were evaluated for diagnostic reason for consultation, rate of multiple pathologist review at the tertiary center, use of immunohistochemistry, and, for private consultation cases, type of sender and concordance with the outside diagnosis. RESULTS: - In the 985 private consultation cases, the most frequent reasons for review were borderline atypia (292 of 878; 33.3%), papillary lesion classification (151 of 878; 17.2%), evaluating invasion (123 of 878; 14%), subtyping carcinoma (75 of 878; 8.5%), and spindle cell (67 of 878; 7.6%) and fibroepithelial (65 of 878; 7.4%) lesion classification. Of 4981 consecutive internal cases, 358 (7.2%) were reviewed, most frequently for borderline atypia (90 of 358; 25.1%), subtyping carcinoma (63 of 358; 17.6%), staging/prognostic features (59 of 358; 16.5%), fibroepithelial lesion classification (45 of 358; 12.6%), evaluating invasion (37 of 358; 10.3%), and papillary (20 of 358; 5.6%) and spindle cell (18 of 358; 5.0%) lesion classification. Of all internal cases, those with a final diagnosis of atypia had a significantly higher rate of review (58 of 241; 24.1%) than those with benign (119 of 2933; 4.1%) or carcinoma (182 of 1807; 10.1%) diagnoses. Immunohistochemistry aided in diagnosis of 39.7% (391 of 985) and 21.2% (76 of 359) of consultation and internally reviewed cases, respectively. CONCLUSIONS: - This study confirms areas of breast pathology that represent diagnostic challenge and supports that pathologists are appropriately using expert consultation.

Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

Cytologic Features and Immunocytochemical Profiles of Malignant Effusions with Metastatic Papillary Thyroid Carcinoma: A Case Series from a Single Institution.

OBJECTIVE: Malignant effusions due to papillary thyroid carcinoma (PTC) are rare, but portend a poor prognosis. PTC metastases, although rare, most frequently occur in the lungs and bone. Therefore, differentiating thyroid etiology of malignant effusions from other sites becomes clinically significant in patient management. This study examines morphologic and immunocytochemical findings in 5 cases of malignant effusions with PTC involvement. STUDY DESIGN: The electronic database at the University of Michigan was searched from January 1, 1995 to December 31, 2014 for malignant pleural effusions with PTC involvement. Clinicopathologic data were obtained from electronic medical records. Cytologic slides were reviewed. RESULTS: Five cases of malignant effusions due to PTC were identified. Characteristic cytologic features of PTC, including ovoid nuclei, irregular nuclear contours, and psammomatous calcifications, were seen. However, the predominant cytologic feature observed was moderate amounts of delicate to vacuolated cytoplasm within the tumor cells. A review of immunocytochemistry demonstrated that all 5 cases showed patchy to diffuse TTF-1 positivity and diffuse positivity for Pax-8. Thyroglobulin only showed focal to patchy positivity in 3 of 5 cases. CONCLUSION: Given the morphologic features found in our case series, an immunocytochemical workup for the evaluation of involvement of an effusion by a thyroid primary is crucial for accurate diagnosis and appropriate clinical treatment.

Utility of estrogen receptor, progesterone receptor, and HER-2/neu analysis of multiple foci in multifocal ipsilateral invasive breast carcinoma.

OBJECTIVES: To determine the frequency of estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu (HER2) testing multiple foci of ipsilateral invasive breast carcinoma at our institution and to evaluate resulting change in treatment recommendation. METHODS: We identified 165 consecutive cases of multifocal invasive breast cancer over a 10-year period (2005-2014). Clinicopathologic features and treatment recommendation were assessed by slide and chart review. RESULTS: Seventy (42.4%) of 165 patients had two or more foci tested. In the first 6 years (2005-2010), frequency of testing two or more foci was 31.6% and increased to 70.6% in 2014. Seven (10%) of 70 had a clinically significant difference in ER/PR and/or HER2 status, five (7.1%) with a difference in HER2, one (1.4%) in ER/PR, and one (1.4%) in both ER/PR and HER2. All cases with difference in status had different histology and/or the largest focus was the most positive one. CONCLUSIONS: Our findings support current recommendations to evaluate additional smaller tumor foci in multifocal invasive breast cancer if the focus is of different grade or histology. Additional features, including specific histology, grade, and ER, PR, and HER2 status of the largest focus, should also be considered when selecting cases for which testing of additional foci may be of benefit.

Young investigator challenge: The utility of GATA3 immunohistochemistry in the evaluation of metastatic breast carcinomas in malignant effusions.

BACKGROUND: It is not uncommon to encounter challenges in the immunohistochemical confirmation of metastatic breast cancer given the limited sensitivities of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15/BRST-2) and the significant proportion of triple-negative breast carcinomas (ie, tumors that are negative for estrogen receptor [ER], and progesterone receptor [PgR], and human epidermal growth factor 2 [HER2]). GATA binding protein 3 (GATA3) has emerged as a potentially useful immunohistochemical adjunct during the evaluation of metastatic breast carcinomas in cytology specimens. The objective of the current study was to examine GATA3 expression in the context of malignant effusions secondary to both mammary and extramammary malignancies. METHODS: In total, 306 malignant effusions (from 62 metastatic breast carcinomas and 244 extramammary malignancies) were examined using GATA3 immunohistochemistry. Effusions with metastatic breast carcinoma were also examined using immunohistochemistry for additional breast markers (ER, PgR, HER2, mammaglobin, and GCDFP-15/BRST-2). RESULTS: GATA3 immunohistochemistry highlighted the tumor cells in 58 of the 62 samples (93.5%) from patients with metastatic breast carcinoma, which was higher than the observed sensitivity of immunohistochemistry for ER (63.8%), PgR (41.4%), HER2 (15.5%), mammaglobin (22.4%), and GCDFP-15/BRST-2 (5.2%). GATA3 expression also was observed in a subset of malignant effusions secondary to extramammary primaries, specifically, in 28 of 244 specimens (11.5%). CONCLUSIONS: GATA3 is a highly sensitive marker for the detection of metastatic breast carcinomas in effusion specimens. However, this marker is not entirely specific for malignancies of breast origin. Thus, GATA3 should be used in conjunction with additional immunohistochemical markers during the cytologic evaluation of malignant effusions.

Metastases to the Pancreas Encountered on Endoscopic Ultrasound-Guided, Fine-Needle Aspiration.

Metastatic lesions in the pancreas are very uncommon and may be difficult to differentiate from the more commonly encountered primary neoplasms derived from the exocrine and endocrine pancreas because of the significant overlap in clinical presentation, imaging, and cytologic features. Metastasis to the pancreas may occur years after treatment of the primary neoplasm and is often not considered on initial evaluation because of the rarity of such events. The possibility of a metastasis to the pancreas should be entertained in patients with any prior history of malignancy because a proper diagnosis is essential in identifying surgical candidates, or avoiding potentially unnecessary surgery and facilitating triage to more appropriate nonoperative therapy. Herein, we describe intrapancreatic metastases secondary to renal cell carcinoma, melanoma, and lung carcinoma, as documented by cytologic examination of endoscopic ultrasound-guided fine-needle aspiration of the pancreatic masses.

Implication of suspicious cytology in endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer.

PURPOSE: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become a preferred technique to evaluate pancreatic masses. The clinical management of a "suspicious for adenocarcinoma" cytological diagnosis is unclear in unresectable cases. We sought to determine whether a suspicious diagnosis in the setting of a high clinical suspicion of malignancy could be sufficient for initiating non-operative therapy, such as chemotherapy, in unresectable patients. METHODS: Twenty-nine solid pancreatic mass cytology specimens obtained by EUS-FNA with a diagnosis of suspicious for adenocarcinoma were identified from 2000 to 2012. Pathology, clinical, and radiologic data were analyzed. RESULTS: Additional procedures were performed in 21 of the 29 patients. Sixteen of the 21 patients had confirmation of malignancy on further tissue sampling and an additional 2 had confirmed unresectable cancers during surgical exploration. Three of the 21 patients had benign diagnoses on subsequent tissue sampling. Of the remaining eight patients who did not undergo additional diagnostic procedures, six were deemed clinically malignant and treated, one died within a year of the EUS-FNA, and one was lost to follow-up. CONCLUSIONS: Consideration of a suspicious diagnosis on EUS-FNA of solid pancreatic masses as sufficient for initiating non-operative therapy is reasonable in the setting of a high clinical suspicion of malignancy.

Value of ultrasound guidance in cytopathologist-performed fine-needle aspirations of palpable lesions.

INTRODUCTION: Fine-needle aspirations (FNAs) of palpable masses are often performed by cytopathologists without ultrasound (US) guidance. Nonetheless, variations in the actual depth of palpable masses lead to occasional challenges. US guidance allows cytopathologists to visualize the mass and guide needle placement. This study retrospectively addressed the utility of US by comparing FNAs performed by cytopathologists on palpable masses with and without US guidance. MATERIALS AND METHODS: Cytopathologist-performed FNAs with and without US guidance from March 1, 2013 to July 1, 2014 were identified. The number of passes, location of lesions, and interpretations were recorded. Available slides were reviewed to determine the proportion of passes that contained diagnostic cellular material and cases in which diagnostic material was present on the first needle pass. RESULTS: In this study, 134 palpation-guided FNAs and 118 US-guided FNAs were analyzed. The percentage of nondiagnostic cases was significantly lower for US-guided FNAs (2.5%) than for palpation-guided FNAs (12.7%; P = 0.004). The average number of needle passes was significantly lower for US-guided FNAs (2.9) than for palpation-guided FNAs (3.6; P = 0.0002). Twenty-two of 118 of US-guided FNAs (18.6%) and 6 of 134 palpation-guided FNAs (4.5%) were completed after only a single pass (P = 0.0008). The percentage of passes with diagnostic material was significantly higher for US-guided FNAs (73.6% versus 60%; P = 0.0002). CONCLUSIONS: For palpable masses, US-guidance adds value to cytopathologists in obtaining diagnostic cellular material more often on the first pass and with fewer passes overall than by palpation alone. This has a potentially beneficial impact on patient care owing to the increased precision and accuracy of needle guidance with ultrasonography.

Ductal carcinoma in situ with distorting sclerosis on core biopsy may be predictive of upstaging on excision.

AIMS: The aim of this study was to examine clinicopathological features of patients with core biopsy diagnoses of ductal carcinoma in situ (DCIS) that may predict invasion on subsequent excision, as upstaging has significant implications regarding the need for axillary staging via sentinel lymph node biopsy (SLNB). METHODS AND RESULTS: We identified 186 patients with a diagnosis of DCIS as the highest-stage lesion on core biopsy. Pathological and clinical features were assessed via slide and chart review, respectively. Distorting sclerosis was defined as irregular angulation of glands involved by DCIS but lacking definite invasion according to histology and/or immunohistochemical staining for myoepithelial markers. Thirty-two of 186 (17.2%) cases had upstaging to either microinvasive (nine) or invasive (23) ductal carcinoma. SLNB was performed in 29 of 32 (90.6%) cases with upstaging and in 55 of 154 (35.7%) cases without (P < 0.0001). Upstaging was significantly associated with the presurgical variables of radiological mass (P = 0.009) and distorting sclerosis (P = 0.0005) and the postsurgical feature of multifocality (P < 0.0001). CONCLUSIONS: Sentinel lymph node biopsy is frequently performed for patients with upstaging from DCIS on core biopsy to microinvasive or invasive carcinoma on excision. DCIS with distorting sclerosis without definite invasion on core biopsy may be predictive of upstaging. This feature may be useful in selecting patients to undergo SLNB at the time of excision to avoid reoperation.

Lobular neoplasia: morphology and management.

CONTEXT: Lobular neoplasia encompasses a spectrum of disease, including atypical lobular hyperplasia and lobular carcinoma in situ. Although classic forms of lobular neoplasia are predominantly heralded as a risk marker, the pleomorphic form of lobular carcinoma in situ is generally regarded as a more aggressive subtype and a possible cancer precursor, and thus is treated in a manner more similar to ductal carcinoma in situ than classic forms of lobular neoplasia. OBJECTIVE: To focus on the morphologic spectrum of lobular neoplasia as highlighted by 3 cases and current management recommendations. Areas of diagnostic challenge and controversy are addressed. DATA SOURCES: A review of the pertinent published literature and current national guidelines was conducted. CONCLUSIONS: Correct classification of classic lobular neoplasia and pleomorphic lobular carcinoma in situ is critical because of differences in clinical management, with current treatment strategies focused on risk reduction for patients with classic lobular neoplasia and eradication of the lesion for those with pleomorphic lobular carcinoma in situ.

Characterization of type III TGF-ß receptor expression in invasive breast carcinomas: a potential new marker and target for triple negative breast cancer.

Invasive breast carcinomas are heterogeneous and exhibit distinct molecular features and biological behavior. Understanding the underlying molecular events that promote breast cancer progression is necessary to improve treatment and prognostication. TGF-ß receptor III (TBR3) is a member of the TGF-ß signaling pathway, with functions in cell proliferation and migration in malignancies, including breast cancer. Recent studies propose that TBR3 may function as a tumor suppressor and that its loss may correlate with disease progression. However, there are limited data on the expression of TBR3 in breast cancer in relationship to tumor type, hormonal receptor status and HER-2/neu, and patient outcome. In this study, we investigated the expression of TBR3 in a cohort of 205 primary invasive breast carcinomas in tissue microarrays (TMAs), with comprehensive clinical, pathological and follow- up information. Sections were stained for TBR3 and evaluated for intensity of reactivity based on a 4-tiered scoring system (1 to 4; TBR3 low = scores 1-2; TBR3 high = scores 3-4). Of the 205 invasive carcinomas, 123 were luminal type (95 type A, 28 type B), 8 were HER-2 type, and 62 were triple negative (TN). TBR3 was high in 112 (55 %) and low in 93 (45 %) cases. Low TBR3 was associated with higher histological grade and worse disease free and overall survival, all features of biologically aggressive breast carcinomas. TBR3 was significantly associated with the subtype of breast cancer, as low TBR3 was detected in 95 % of TN compared to 22 % of luminal tumors (p < 0.0001). We discovered a significant association between low TBR3 protein expression, TN breast cancer phenotype, and disease progression. These data suggest that TBR3 loss might be linked to the development of TN breast cancers and pave the way to investigating whether restoring TBR3 function may be a therapeutic strategy against TN breast carcinomas.

Pancreatic neuroendocrine tumors: accurate grading with Ki-67 index on fine-needle aspiration specimens using the WHO 2010/ENETS criteria.

BACKGROUND: The natural history of pancreatic neuroendocrine tumors (panNETs) is extremely variable. One of the most controversial problems in diagnosis is the accurate prediction of the clinical behavior of these tumors. PanNETs that behave aggressively with a malignant course may have bland cytologic features, while some tumors with previously described "malignant" features may behave in a benign or indolent fashion. Various classification schemes have been proposed for grading panNETs. The European Neuroendocrine Tumor Society (ENETS) and 2010 World Health Organization (WHO) classification schemes include counting the mitotic index and/or the Ki-67 proliferation index for grading. The current study was undertaken to determine whether tumors sampled by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can be accurately graded based on the Ki-67 index when compared to surgical samples. METHODS: Corresponding EUS-FNA cytology and surgical tissue specimens were obtained for 22 tumors and stained for hematoxylin and eosin (H&E) and the Ki-67 proliferation marker (MIB-1 antibody). Samples were graded by scoring Ki-67 staining indices in accordance with the 2010 ENETS/WHO criteria. The grading scores assigned to the EUS-FNA cytology samples were compared with the scores assigned to the corresponding histological samples. RESULTS: The majority (86%) of EUS-FNA cytology samples and corresponding surgical tissue specimens demonstrated concordant grading based on Ki-67 indices. CONCLUSIONS: These results indicate that EUS-FNA cytology samples can be accurately graded based on the WHO Ki-67 labeling scheme. Thus, Ki-67 scoring in EUS-FNA cytology samples is an alternative approach for establishing the grade of panNETs. Accurate grading of panNETs is critical for predicting tumor biology, patient prognosis, and making informed decisions regarding patient management and treatment.

Re-excision rates of invasive ductal carcinoma with lobular features compared with invasive ductal carcinomas and invasive lobular carcinomas of the breast.

BACKGROUND: Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies. METHODS: Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed. RESULTS: For T2 tumors (2.1-5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L. CONCLUSIONS: Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.

Fine needle aspiration of primary mediastinal synovial sarcoma: cytomorphologic, immunohistochemical, and molecular study.

The cytologic diagnosis of synovial sarcoma (SS) can be difficult when it occurs in unusual locations, atypical age groups, and/or have unusual morphology. We report a case of primary mediastinal SS in a 65-year-old male with a long smoking history who presented with increasing shortness of breath and was found to have a 14.2 cm mediastinal mass. Smears from the endobronchial ultrasound guided fine needle aspiration of the mass were moderately cellular consisting of loosely cohesive clusters, some of which demonstrated nuclear molding, and dispersed single cells. The relatively uniform tumor cells had a high nuclear-to-cytoplasmic ratio, finely granular chromatin, and inconspicuous nucleoli. Some of the single cells had spindled morphology with unipolar wispy tails and naked nuclei. Based on the clinical presentation and the cytomorphologic features, our initial differential diagnoses included atypical carcinoid, small cell carcinoma, basaloid squamous cell carcinoma, sarcoma, and lymphoma. Immunohistochemical studies on the cell block sections revealed that the tumor cells were focally positive for cytokeratin and diffusely positive for CD56, while negative for CD45, synaptophysin and chromogranin. Ultimately, an immunohistochemical stain for TLE-1 demonstrated diffusely strong nuclear positivity and molecular studies showed the presence of the t(X; 18) SYT/SSX1 translocation confirming the diagnosis of SS. In this report, we describe the cytomorphologic features of SS, its diagnostic pitfalls, and potential mimics in the mediastinum.

Invasive ductal carcinoma with lobular features: a comparison study to invasive ductal and invasive lobular carcinomas of the breast.

Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a distinct subtype of breast cancer, and its clinicopathologic features and outcomes are unknown. In this retrospective study, we focused on characterization of clinicopathologic features and outcomes of IDC-L and compared them to invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC. Available slides of IDC-L (n = 150) were reviewed to quantify the lobular component (≤ 20, 21-50, 51-80, >80 %), defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests. E-cadherin immunostain was performed to confirm ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic grade (p < 0.001), be positive for estrogen receptor (96 vs. 70 %; p < 0.0001) and progesterone receptor (84 vs. 57 %; p < 0.0001), and less likely to overexpress HER-2/neu (12 vs. 23 %; p = 0.001). Despite these favorable prognostic features, IDC-L had a higher frequency of nodal metastases (51 vs. 34 %; p < 0.0001) and a worse 5-year disease-free survival than IDC (hazard ratio = 0.454; p = 0.0004). ILC and IDC-L had similar clinicopathologic features and outcomes. The proportion of the lobular component in IDC-L had no impact on the size, nodal status, stage, or outcome. Our data suggest that although IDC-L may be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical and biological characteristics are more similar to that of ILC.

The role of cytology in the preoperative assessment and management of patients with pancreaticobiliary tract neoplasms.

OBJECTIVE: Endoscopic ultrasound-guided fine-needle aspiration and bile duct brushings are utilized in the cytologic evaluation of solid and cystic pancreaticobiliary tract lesions. We sought to determine the diagnostic accuracy of cytology. METHODS: Five hundred seventy-nine pancreatic resections with 727 corresponding cytology specimens were identified from 1997 to 2012. Histologic diagnoses included benign, carcinoma, pancreatic endocrine neoplasm (PEN), nonepithelial neoplasms, cystic neoplasms, and ampullary adenomas. Standard interpretative categories-nondiagnostic, negative, atypical, suspicious, and positive--were utilized for preoperative cytology specimens. RESULTS: For solid masses, the sensitivity and specificity of positive fine-needle aspiration (FNA) cytology for detecting carcinoma were 74 and 100 %, respectively. FNAs performed better than brushings (sensitivity, 40 %; specificity, 98 %) in detecting carcinomas. Similar findings were seen for PENs and nonepithelial neoplasms. For cystic lesions, the sensitivity of FNA for predicting malignancy was lower (24 %) with a specificity of 97 %. Sequentially combining suspicious and atypical categories with the positive category resulted in increases in sensitivity and decreases in specificity for all cases except for cystic lesions. CONCLUSIONS: Cytology adds to the assessment of solid masses, but its utility in cystic lesions is less clear. Consideration of a suspicious cytologic interpretation as a positive diagnosis for triaging patients to surgery is supported by our study.